S. W. Lee and S. I. Fried. 6/6/2022. “Micro-magnetic stimulation of primary visual cortex induces focal and sustained activation of secondary visual cortex.” Philosophical Transactions of the Royal Society A, 380, 2228, Pp. 20210019. Publisher's VersionAbstract
Cortical visual prostheses that aim to restore sight to the blind require the ability to create neural activity in the visual cortex. Electric stimulation delivered via microelectrodes implanted in the primary visual cortex (V1) has been the most common approach, although conventional electrodes may not effectively confine activation to focal regions and thus the acuity they create may be limited. Magnetic stimulation from microcoils confines activation to single cortical columns of V1 and thus may prove to be more effective than conventional microelectrodes, but the ability of microcoils to drive synaptic connections has not been explored. Here, we show that magnetic stimulation of V1 using microcoils induces spatially confined activation in the secondary visual cortex (V2) in mouse brain slices. Single-loop microcoils were fabricated using platinum-iridium flat microwires, and their effectiveness was evaluated using calcium imaging and compared with that of monopolar and bipolar electrodes. Our results show that compared to the electrodes, the microcoils better confined activation to a small region in V1. In addition, they produced more precise and sustained activation in V2. The finding that microcoil-based stimulation propagates to higher visual centres raises the possibility that complex visual perception, e.g. that requiring sustained synaptic inputs, may be achievable. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.
H.T. Le, R.I. Haque, Z. Ouyang, S. W. Lee, S. I. Fried, D. Zhao, M. Qiu, and A. Han. 8/11/2021. “MEMS inductor fabrication and emerging applications in power electronics and neurotechnologies.” Microsystems & Nanoengineering, 7, 59, Pp. 1-22. Publisher's Version
S. W. Lee and S. I. Fried. 5/18/2021. “Selective activation of cortex using bent micro-wires to magnetically stimulate neurons.” United States of America US 11,007,372 B2 (U.S Patent).
A.C. Paulk, J.C. Yang, D. R. Cleary, D. J. Soper, M. Halgren, A. R. O'Donnell, S. H. Lee, M. Ganji, Y. G. Ro, H. Oh, L. Hossain, J. Lee, Y. Tchoe, N. Rogers, K. Kiliç, S. B. Ryu, S. W. Lee, J. Hermiz, V. Gilja, I. Ulbert, D. Fabó, O. Devinsky, J.R. Madsen, E.N. Eskandar, J. W. Lee, D. Maus, A. Devor, S. I. Fried, P. S. Jones, B. V. Nahed, S. Ben-Haim, S. K. Bick, R. Richardson, A. M. T. Raslan, D. A. Siler, D. P. Cahill, Z. M. Williams, G. R. Cosgrove, S. A. Dayeh, and S. S. Cash. 3/22/2021. “Microscale Physiological Events on the Human Cortical Surface.” Cerebral Cortex. Publisher's Version
S. W. Lee. 10/23/2020. “Selective activation of cortical columns using multichannel magnetic stimulation with a bent flat microwire array.” IEEE Transactions on Biomedical Engineering. Publisher's Version
S. B. Ryu, A.C. Paulk, J.C. Yang, M. Ganji, S. A. Dayeh, S. S. Cash, S. I. Fried, and S. W. Lee. 10/21/2020. “Spatially confined responses of mouse visual cortex to intracortical magnetic stimulation from micro-coils.” Journal of Neural Engineering, 17, 5, Pp. Article 056036. Publisher's VersionAbstract
Objective: Electrical stimulation via microelectrodes implanted in cortex has been suggested as a potential treatment for a wide range of neurological disorders. Despite some success however, the effectiveness of conventional electrodes remains limited, in part due to an inability to create specific patterns of neural activity around each electrode and in part due to challenges with maintaining a stable interface. The use of implantable micro-coils to magnetically stimulate the cortex has the potential to overcome these limitations because the asymmetric fields from coils can be harnessed to selectively activate some neurons, e.g. vertically-oriented pyramidal neurons while avoiding others, e.g. horizontally-oriented passing axons. In vitro experiments have shown that activation is indeed confined with micro-coils but their effectiveness in the intact brain of living animals has not been evaluated. Approach: To assess the efficacy of stimulation, a 128-channel custom recording microelectrode array was positioned on the surface of the visual cortex (ECoG) in anesthetized mice and responses to magnetic and electric stimulation were compared. Stimulation was delivered from electrodes or micro-coils implanted through a hole in the center of the recording array at a rate of 200 pulses per second for 100 ms. Main results: Both electric and magnetic stimulation reliably elicited cortical responses, although activation from electric stimulation was spatially expansive, often extending more than 1 mm from the stimulation site, while activation from magnetic stimulation was typically confined to a ~300 µm diameter region around the stimulation site. Results were consistent for stimulation of both cortical layer 2/3 and layer 5 as well as across a range of stimulus strengths. Significance: The improved focality with magnetic stimulation suggests that the effectiveness of cortical stimulation can be improved. Improved focality may be particularly attractive for cortical prostheses that require high spatial resolution, e.g. devices that target sensory cortex, as it may lead to improved acuity.
H. Yu, S. Enayati, K. Chang, K. Cho, S. W. Lee, M. Talib, K. Zihlavnikova, J. Xie, H. Achour, S. I. Fried, T. P. Utheim, and D. F. Chen. 4/9/2020. “Noninvasive Electrical Stimulation Improves Photoreceptor Survival and Retinal Function in Mice with Inherited Photoreceptor Degeneration.” Investigative Ophthalmology & Visual Science, 61, 4, Pp. Article 5. Publisher's Version
M. Ganji, A. Paulk, J. Yang, N. Vahidi, S. H. Lee, R. Liu, L. Hossain, E. Arneodo, M. Thunemann, M. Shigyo, A. Tanaka, S. B. Ryu, S. W. Lee, Y. Tchoe, M. Marsala, A. Devor, D. Cleary, J. Martin, H. Oh, V. Gilja, T. Gentner, S. I. Fried, E. Halgren, S. S. Cash, and S. A. Dayeh. 8/1/2019. “Selective Formation of Porous Pt Nanorods for Highly Electrochemically Efficient Neural Electrode Interfaces.” Nano Letters, 19, 9. Publisher's VersionAbstract
The enhanced electrochemical activity of nanostructured materials is readily exploited in energy devices, but their utility in scalable and human-compatible implantable neural interfaces can significantly advance the performance of clinical and research electrodes. We utilize low-temperature selective dealloying to develop scalable and biocompatible 1D platinum nanorod (PtNR) arrays that exhibit superb electrochemical properties at various length scales, stability, and biocompatibility for high performance neurotechnologies. PtNR arrays record brain activity with cellular resolution from the cortical surfaces in birds and non-human primates. Significantly, strong modulation of surface recorded single unit activity by auditory stimuli is demonstrated in European Starling birds as well as the modulation of local field potentials in the visual cortex by light stimuli in a non-human primate, and as well as responses to electrical stimulation in mice. PtNRs record behaviorally and physiologically relevant neuronal dynamics from the surface of the brain with high spatiotemporal resolution which paves the way for less invasive brain-machine interfaces.
S. W. Lee, K. Thyagarajan, and S. I. Fried. 6/1/2019. “Micro-coil design influences the spatial extent of responses to intracortical magnetic stimulation.” IEEE Transactions on Biomedical Engineering, 66, 6, Pp. 1680 - 1694. Publisher's Version
M. Zaeimbashi, Z. Wang, S. W. Lee, S. S. Cash, S. I. Fried, and N. Sun. 10/29/2018. “Micro-solenoid inductors with magnetic core for neural stimulation.” 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). Honolulu, HI, USA, USA. Publisher's Version
S. I. Fried and S. W. Lee. 6/12/2018. “Magnetic neural stimulator and method of activation of neural tissue with same.” United States of America US 9,993,656 B2 (U.S. Patent).
D. K. Freeman, J. M. O’Brien, P. Kumar, B. Daniels, R. A. Irion, L. Shraytah, B. K. Ingersoll, A. P. Magyar, A. Czarnecki, J. Wheeler, J. R. Coppeta, M. P. Abban, R. Gatzke, S. I. Fried, S. W. Lee, A. E. Duwel, J. J. Bernstein, A.S. Widge, A. Hernandez-Reynoso, A. Kanneganti, M. I. Romero-Ortega, and S. F. Cogan. 11/27/2017. “A Sub-millimeter, Inductively Powered Neural Stimulator.” Frontiers in Neuroscience, 11, 659. Publisher's Version
S. W. Lee and S. Fried. 9/2/2017. “Enhanced control of cortical pyramidal neurons with micromagnetic stimulation.” IEEE Trans Neural Syst Rehabil Eng, 25, 9, Pp. 1375-1386. Publisher's VersionAbstract
Magnetic stimulation is less sensitive to the inflammatory reactions that plague conventional electrode-based cortical implants and therefore may be useful as a next-generation (implanted) cortical prosthetic. The fields arising from micro-coils are quite small however and thus, their ability to modulate cortical activity must first be established. Here, we show that layer V pyramidal neurons (PNs) can be strongly activated by micro-coil stimulation and further, the asymmetric fields arising from such coils do not simultaneously activate horizontally -oriented axon fibers, thus confining activation to a focal region around the coil. The spatially-narrow fields from micro-coils allowed the sensitivity of different regions within a single PN to be compared: while the proximal axon was most sensitive in naive cells, repetitive stimulation over the apical dendrite led to a change in state of the neuron that reduced thresholds there to below those of the axon. Thus, our results raise the possibility that regardless of the mode of stimulation, penetration depths that target specific portions of the apical dendrite may actually be more effective than those that target Layer 6. Interestingly, the state change had similar properties to state changes described previously at the systems level, suggesting a possible neuronal mechanism underlying such responses.
S. W. Lee and S. I. Fried. 8/22/2017. “Precise and Reliable Activation of Cortex with Micro-coils.” In Brain-Computer Interface Research, Pp. 21-33. Springer International Publishing. Publisher's Version
S. I. Fried and S. W. Lee. 7/1/2017. “Towards an improved understanding of the sensitivity of cortical neurons to stimulation.” Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, 10, 4, Pp. e32. Publisher's Version
S. W. Lee, F. Fallegger, B. D. Casse, and S. I. Fried. 2016. “Implantable microcoils for intracortical magnetic stimulation.” Science Advances, 2, Pp. e1600889.Abstract
Neural prostheses that stimulate the neocortex have the potential to treat a wide range of neurological disorders. However, the efficacy of electrode-based implants remains limited, with persistent challenges that include an inability to create precise patterns of neural activity as well as difficulties in maintaining response consistency over time. These problems arise from fundamental limitations of electrodes as well as their susceptibility to implantation and have proven difficult to overcome. Magnetic stimulation can address many of these limitations, but coils small enough to be implanted into the cortex were not thought strong enough to activate neurons. We describe a new microcoil design and demonstrate its effectiveness for both activating cortical neurons and driving behavioral responses. The stimulation of cortical pyramidal neurons in brain slices in vitro was reliable and could be confined to spatially narrow regions (<60 mum). The spatially asymmetric fields arising from the coil helped to avoid the simultaneous activation of passing axons. In vivo implantation was safe and resulted in consistent and predictable behavioral responses. The high permeability of magnetic fields to biological substances may yield another important advantage because it suggests that encapsulation and other adverse effects of implantation will not diminish coil performance over time, as happens to electrodes. These findings suggest that a coil-based implant might be a useful alternative to existing electrode-based devices. The enhanced selectivity of microcoil-based magnetic stimulation will be especially useful for visual prostheses as well as for many brain-computer interface applications that require precise activation of the cortex.
S. I. Fried and S. W. Lee. 2016. “Responses of L5 pyramidal neurons of V1 to electrical stimulation.” Invest Ophthalmol Vis Sci, 57, Pp. 5328-5328.Abstract
Abstract Purpose : Direct electrical stimulation of primary visual cortex (V1) has been proposed as a means to restore vision to the blind. Despite some success in eliciting visual perception in human subjects as well as in non-human primates, a well-reasoned stimulation strategy has not been developed. For example, it is not known whether certain layers of V1 are more sensitive to electric stimulation than others nor are the responses of specific neuronal types to stimulation well understood. Here we measured the responses of L5 pyramidal neurons in vitro to stimulation from electrodes positioned at different cortical depths. Methods : Cell-attached patch clamp was used to record spikes from L5 pyramidal neurons of V1 in an in vitro mouse brain slice preparation. Single conical-shaped platinum/iridium stimulating electrodes with impedance of 1 MΩ were positioned such that the electrode tip was initially centered directly above the soma of a targeted cell. Stimulus waveforms were cathodic-first biphasic current pulses with a pulse duration of 200 µs and no interphase intervals. Stimulation was delivered at a frequency of 200 Hz for 0.1 s (20 total pulses). The amplitude of stimulation ranged from 0 to 30 μA. Measurements were repeated as the electrode tip was translated in 100 µm steps along the apical dendrite of targeted neurons as well as along the axon. Results : The strongest responses (highest spike counts) were elicited when the electrode tip was positioned close to the soma (layer 5 – 6); latencies for these spikes were 0.2 - 0.4 ms. Average thresholds were 14.09 µA (STDEV: 4.83 µA). Fewer spikes were elicited when the electrode was positioned over the distal apical dendrites (layer 1 – 4), even at amplitude levels of 30 µA (the maximum that could be delivered in our system). Interestingly, spikes arising from stimulation over the apical dendrite were bigger and sharper and had longer latencies (1-2 ms) than those that arose from stimulation over the axon (layers 5 – 6). Conclusions : Our results suggest that L5 pyramidal neurons of V1 are maximally sensitive to stimulation over deeper cortical layers (5 – 6). Moreover, the results also suggest that electrode position can alter the spike shape. Therefore, electrode depth is not only important for threshold optimization, but also, the depth of penetration may also contribute to distinct visual percepts. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
S. W. Lee and S. I. Fried. 2015. “Magnetic control of cortical pyramidal neuron activity using a micro-coil.” 2015 7th International IEEE/EMBS Conference on Neural Engineering (NER).
S. W. Lee and S. I. Fried. 2015. “Suppression of subthalamic nucleus activity by micromagnetic stimulation.” IEEE Trans Neural Syst Rehabil Eng, 23, Pp. 116-27.Abstract
Magnetic stimulation delivered via 0.5-mm diameter coils was recently shown to activate retinal neurons; the small coil size raises the possibility that micromagnetic stimulation ( muMS) could underlie a new generation of implanted neural prosthetics. Such an approach has several inherent advantages over conventional electric stimulation, including the potential for selective activation of neuronal targets as well as less susceptibility to inflammatory responses. The viability of muMS for some applications, e.g., deep brain stimulation (DBS), may require suppression (rather than creation) of neuronal activity, however, and therefore we explore here whether (muMS) could, in fact, suppress activity. While single pulses elicited weak and inconsistent spiking in neurons of the mouse subthalamic nucleus (in vitro), repetitive stimulation effectively suppressed activity in approximately 70% of targeted neurons. This is the same percentage suppressed by conventional electric stimulation; with both modalities, suppression occurred only after an initial increase in spiking. The latency to the onset of suppression was inversely correlated to the energy of the stimulus waveform: larger amplitudes and lower frequencies had the fastest onset of suppression. These findings continue to support the viability of muMS as a next-generation implantable neural prosthetic.
S.J. Kim, S. W. Lee, C. J. Lee, and S. K. An. 11/11/2014. “Micro-electrode array package using liquid crystal polymer and manufacturing method thereof.” United States of America US 8,886,277 B2 (U.S. Patent).